Alzheimer's presenilin 1 causes chromosome missegregation and aneuploidy

Debrah I. Boeras, Antoneta Granic, Jaya Padmanabhan, Nichole C. Crespo, Amyn Mohammed Rojiani, Huntington Potter

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Mutations in the presenilin 1 gene cause most early onset familial Alzheimer's disease (FAD). Here, we report that a defect in the cell cycle - improper chromosome segregation - can be caused by abnormal presenilin function and therefore may contribute to AD pathogenesis. Specifically we find that either over-expression or FAD mutation in presenilin 1 (M146L and M146V) leads to chromosome missegregation and aneuploidy in vivo and in vitro: (1) Up to 20% of lymphocytes and neurons of FAD-PS-1 transgenic and knockin mice are aneuploid by metaphase chromosome analysis and in situ hybridization. (2) Transiently transfected human cells over-expressing normal or mutant PS-1 develop similar aneuploidy within 48 h, including trisomy 21. (3) Mitotic spindles in the PS-1 transfected cells contain abnormal microtubule arrays and lagging chromosomes. Several mechanisms by which chromosome missegregation induced by presenilin may contribute to Alzheimer's disease are discussed.

Original languageEnglish (US)
Pages (from-to)319-328
Number of pages10
JournalNeurobiology of Aging
Volume29
Issue number3
DOIs
StatePublished - Mar 1 2008

Fingerprint

Presenilin-1
Aneuploidy
Alzheimer Disease
Chromosomes
Presenilins
Chromosome Segregation
Mutation
Spindle Apparatus
Metaphase
Down Syndrome
Microtubules
Transgenic Mice
In Situ Hybridization
Cell Cycle
Lymphocytes
Neurons
Genes

Keywords

  • Alzheimer's disease
  • Chromosome segregation
  • Down syndrome
  • Microtubules
  • Mitosis
  • Presenilin
  • Trisomy 21

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Alzheimer's presenilin 1 causes chromosome missegregation and aneuploidy. / Boeras, Debrah I.; Granic, Antoneta; Padmanabhan, Jaya; Crespo, Nichole C.; Rojiani, Amyn Mohammed; Potter, Huntington.

In: Neurobiology of Aging, Vol. 29, No. 3, 01.03.2008, p. 319-328.

Research output: Contribution to journalArticle

Boeras, Debrah I. ; Granic, Antoneta ; Padmanabhan, Jaya ; Crespo, Nichole C. ; Rojiani, Amyn Mohammed ; Potter, Huntington. / Alzheimer's presenilin 1 causes chromosome missegregation and aneuploidy. In: Neurobiology of Aging. 2008 ; Vol. 29, No. 3. pp. 319-328.
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